Abstract : CD5(+) B lymphocytes have distinct functional properties compared with B lymphocytes that lack CD5. However, it remains unclear if and how the CD5 molecule modulates B lymphocyte biology and responses. Our recent studies have revealed that CD5 promotes constitutive activation of multiple signaling pathways including extracellular signal-regulated kinases (ERK1/2), phosphatidylinositol 3-kinase (PI-3K)/mammalian target of rapamycin (mTOR) and calcineurin-NFAT signaling pathways. Further, changes in cytokine production including the production of IL-10 are related to the activation of the transcription factors NFAT2 and STAT3. All in all, these studies provide a framework for understanding how CD5 impacts B lymphocyte biology and responses.